title: Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and apoptosis induction.
abstract: Isoalantolactone is a sesquiterpene lactone compound isolated from the roots of Inula helenium L. Previous studies have demonstrated that isoalantolactone possesses antifungal, anti-bacterial, anti-helminthic and anti-proliferative properties in a variety of cells, but there are no studies concerning its effects on head and neck squamous cell carcinoma (HNSCC). In the present study, an MTT assay demonstrated that isoalantolactone has anti-proliferative activity against the HNSCC cell line (UM-SCC-10A). Immunostaining identified that this compound induced UM-SCC-10A cell apoptosis but not necrosis. To explain the molecular mechanisms underlying its effects, flow cytometry and western blot analysis showed that the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and p21, and down-regulation of cyclin D. Furthermore, our results revealed that induction of apoptosis through a mitochondrial pathway led to up-regulation of pro-apoptotic protein expression (Bax), down-regulation of anti-apoptotic protein expression (Bcl-2), mitochondrial release of cytochrome c (Cyto c), reduction of mitochondrial membrane potential (MMP) and activation of caspase-3 (Casp-3). Involvement of the caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. Together, our findings suggest that isoalantolactone induced caspase-dependent apoptosis via a mitochondrial pathway and was associated with cell cycle arrest in the G1 phase in UM-SCC-10A cells. Therefore, isoalantolactone may become a potential drug for treating HNSCC.
authors.affiliation: Department of Cell Biology and Anatomy, Liaoning Medical University, Jinzhou, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiehua
authors.initials: J
authors.lastname: Hu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Weng
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
authors.forename: Fu
authors.initials: F
authors.lastname: Ren
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056741:Cyclin D / Q000378:metabolism; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D056741:Cyclin D; D012717:Sesquiterpenes; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C032787:isoalantolactone; D020741:rho GTP-Binding Proteins; C022616:thiazolyl blue